The goals of this project Include the analysis of molecular genetic alterations in human endometrial carcinoma and endometriosis. Using both cell lines and primary human tissue samples, the oncogene Ki-ras and the putative tumor suppressor gene DCC were shown to have a potential role in endometrial carcinoma. In addition, procedures were developed that allow for the detection of the somatic nature of these genetic alterations, by using archival, paraffin-embedded tissue specimens. This procedures will allow for the screening of large numbers of tissue samples, for which retrospective data exist concerning various risk factors, such as excessive hormonal exposure. Collaborations were established that allowed access to tumor samples from patients in "endometrial cancer families" and other hereditary conditions that potentially predispose affected individuals to endometrial and colon tumors. Analysis of these tumors is expected to yield further insight into the genetics of human endometrial cancer development. Similar strategies will be employed to evaluate a potential molecular genetic basis of endometriosis. Endometriosis is a non-malignant condition of aberrant endometrial tissue growth and is likely related to pelvic pain and infertility in 10-15% of the premenopausal U.S. population. Primary tissue samples and paraffin blocks have been obtained through collaborative arrangements with local medical institutions, and studies of gene expression in these samples are underway.